1. Field of the Invention
The present invention is in the field of nutrition. More specifically, the present invention is directed to methods of measuring protein and/or fat digestibility and uses thereof.
2. Description of the Related Art
Malabsorption of nutrients due to exocrine pancreatic insufficiency is a main factor contributing to weight loss or poor weight gain in patients with cystic fibrosis (CF) leading to deficiencies of essential nutrients. Although it is well established that fat digestibility is impaired in cystic fibrosis, the prior art methods to measure protein digestibility are limited and often not accurate. As impaired protein digestibility leads to an impaired anabolic response to a meal as well as to high loads of undigested proteins in the colon, which induce diarrhea and the production of harmful toxins by gut bacteria, accurate quantification of protein digestibility is of high clinical importance in cystic fibrosis.
Many decades ago, a diminished retention of dietary proteins in cystic fibrosis was demonstrated with nitrogen balance tests and stool analyses, methods with limited accuracy that are too laborious and time consuming for routine diagnostic use. In 1952, a simpler and accurate method was developed using oral ingestion of 131I-labeled protein. 13C intrinsically labeled milk or egg proteins has been used to assess protein digestibility by measuring the enrichment kinetics of labeled CO2 in the breath in response to meal intake. A limitation of this method is the difficulty to obtain large amounts of proteins with sufficiently high amino acid enrichment levels and with adequate labeling patterns, making production of these labeled proteins cumbersome and expensive. Furthermore, the accuracy of using 13C-intrinsically labeled milk or egg protein, or even uniformly 13C-labeled algal protein and measuring 13CO2 production might be limited in cystic fibrosis as these patients are characterized by chronic and acute episodes of lung inflammation which contribute to CO2 production in the breath and changes in the CO2 pool size.
Reduced digestion capacity of nutrients due to exocrine pancreatic insufficiency (EPI) is an important disease-related factor contributing to weight loss. Severe exocrine pancreatic insufficiency impairs the digestion of fat, carbohydrate and protein leading to nutrient deficiencies. Current dietary recommendations comprise a high energy (>120% of recommended daily allowances), high fat and high protein diet (40% and 15%, respectively). Since high dietary fat is the main energy source for patients with cystic fibrosis, fat absorption is currently the marker of effective nutrient digestion in cystic fibrosis patients. In addition, providing an appropriate dose and good timing of Pancreatic Enzyme Replacement Therapy (PERT) is of crucial importance to increase lipid digestibility and systemic lipid availability in CF.
In refractory patients who do not respond to Pancreatic Enzyme Replacement Therapy, fecal energy content and fecal fat balance study is the non-invasive gold standard method to assess pancreatic exocrine function by measuring the consequence of reduced fat digestion and absorption. This technique is based on a measurement of triglycerides in feces during a three day collection period and careful determination of fat intake to be able to calculate the fat balance. In daily practice, the appropriate dose of Pancreatic Enzyme Replacement Therapy is determined on clinical ground (symptoms and weight gain) alone, because the fecal fat balance test is unpleasant, unpractical, and cumbersome.
No information is available regarding the acute effect of Pancreatic Enzyme Replacement Therapy on lipid digestion in CF, which is of particular importance in patients who receive continuous night time gastro-intestinal tube feeding. When pancreatic enzymes are given at the beginning of enteral feeding, the duration of enzyme activity, absolute necessity and timing of a second dose, and appropriate dose to improve fat digestion are unknown. Because the current standard technique measures over a 72-hour period, this technique represents a long term fat digestion and absorption capacity and cannot be used to measure acute changes in fat digestibility. Thus, there is no established technique available to measure acute fat digestibility in CF.
Techniques that use carbon-labeled radioactive or stable isotope fatty acids have been described, measuring the labeled CO2 production after ingestion of the labeled fatty acids. These methods have been used in patients with CF to detect fat malabsorption and to monitor the efficacy of Pancreatic Enzyme Replacement Therapy. However these methods have several disadvantages (e.g., the results are a combination of the process of fat digestion and absorption, and are related to metabolism and oxidation of fatty acids to CO2 in the body) and therefore are not used anymore to calculate fat uptake in CF.
The prior art is deficient in techniques for the measurement of protein and/or fat digestibility. The present invention fulfills this longstanding need and desire in the art.